Electroosmotic tissue treatment

ABSTRACT

Apparatus for driving fluid between first and second anatomical sites of a subject is provided, comprising (1) a first electrode, configured to be coupled to the first anatomical site of the subject; (2) a second electrode, configured to be coupled to the second anatomical site of the subject; and (3) a control unit, configured to (i) detect a pressure difference between the first and second anatomical sites, and (ii) in response to the detected pressure difference, drive fluid between the first and second anatomical sites by applying a treatment voltage between the first and second electrodes. Other embodiments are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is related to U.S. patent application Ser. No.13/663,757 to Gross, filed Oct. 30, 2012, titled “Iontophoretic andelectroosmotic disc treatment”, which published as US 2013/0102952 nowU.S. Pat. No. 8,676,348); which is a Continuation of U.S. patentapplication Ser. No. 12/373,306 to Gross, which published as US2009/0312816 (now U.S. Pat. No. 8,577,469); which is a US National Phaseof PCT patent application PCT/IL07/00865 to Gross, filed Jul. 10, 2007,titled “Iontophoretic and electroosmotic disc treatment”, whichpublished as WO 2008/007369; which claims priority from U.S. provisionalpatent application 60/830,717 to Gross, filed Jul. 12, 2006, titled“Iontophoretic and electroosmotic disc treatment”, all of which areincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to medical devices, andspecifically to apparatus and methods for increasing the throughput offluid through a tissue or otherwise modifying the fluid balance in atissue.

BACKGROUND

Many ailments originate from excess fluid in tissues, e.g., due toinsufficient or damaged drainage of fluid from the tissue. As a result,this fluid causes elevated pressure in the tissue, which may result indiscomfort and/or tissue damage. Examples of tissues prone to thisproblem are the brain, kidneys, lymph nodes, and eyes.

For hydrocephalus (i.e., the abnormal accumulation of cerebrospinalfluid in the ventricles of the brain), a common treatment approach is touse a shunt, which includes a drainage tube and a valve that controlsthe volume and rate of cerebrospinal fluid outflow from the brain toanother part of the body (e.g., the abdomen).

SUMMARY OF THE INVENTION

Techniques are described for electroosmotically driving fluid between afirst tissue of a subject and a second tissue of the subject. For someapplications, the fluid is driven in response to detecting a pressure atleast one of the tissues, and/or a pressure difference between thetissues. For some applications, the pressure difference is detected bydetecting a voltage, such as a streaming potential, between the tissues.

For some applications of the present invention, a system for increasingthe throughput of fluid in the brain is provided. Typically, a firstelectrode is coupled to the superior sagittal sinus of the subject, anda second electrode is coupled to the cerebral cortex of the subject.According to one application of the present invention, a control unit,coupled to the electrodes, is configured to apply a voltage between thefirst and second electrodes, and to configure the voltage toelectroosmotically drive fluid from the superior sagittal sinus to thecerebral cortex.

For some applications of the present invention, a system for increasingthe throughput of fluid in the kidney is provided. Typically, a firstelectrode is coupled to the renal artery of the subject, and a secondelectrode is coupled to the ureter of the subject. According to oneapplication of the present invention, the control unit is configured toapply a voltage between the first and second electrodes, and toconfigure the voltage to electroosmotically drive fluid from the renalartery to the ureter.

For some applications of the present invention, a system for increasingthe throughput of fluid in a lymph node is provided. Typically, a firstelectrode is coupled to the artery entering the lymph node of thesubject, and a second electrode is coupled to the medullary sinus of thelymph node. According to one application of the present invention, thecontrol unit is configured to apply a voltage between the first andsecond electrodes, and to configure the voltage to electroosmoticallydrive fluid from the artery entering the lymph node to the medullarysinus.

For some applications of the present invention, a system for increasingthe throughput of fluid in the eye is provided. Typically, a firstelectrode is coupled to a vitreous cavity of the eye of the subject, anda second electrode is coupled to a Schlemm's canal of the subject.According to one application of the present invention, the control unitis configured to apply a voltage between the first and secondelectrodes, and to configure the voltage to electroosmotically drivefluid from the vitreous cavity to the Schlemm's canal.

For some applications of the present invention, a system for drivingfluid between a nucleus pulposus of an intervertebral disc and a siteoutside of the nucleus pulposus is provided. Typically, a firstelectrode is coupled to (e.g., inserted into) the nucleus pulposus ofthe subject, and a second electrode is coupled to the site outside ofthe nucleus pulposus (e.g., to an outer surface of an annulus fibrosusof the intervertebral disc). According to one application of the presentinvention, the control unit is configured to apply a voltage between thefirst and second electrodes, and to configure the voltage toelectroosmotically drive fluid from the site outside of the nucleuspulposus, to the nucleus pulposus.

For some applications of the present invention, electroosmosis isperformed using insulated electrodes. Typically, when the control unitapplies a voltage between the electrodes, a capacitance-based currentflows toward one of the electrodes, resulting in fluidelectroosmotically moving from one site to another. For example, thistechnique may be practiced to drive fluid in any of the sites describedhereinabove.

It is noted that, for some applications, electroosmosis techniques asprovided herein can be performed anywhere in a body of the subject whereionic filtration occurs.

There is further provided, in accordance with an application of thepresent invention, apparatus for driving fluid between first and secondanatomical sites of a subject, the apparatus including:

a first electrode, configured to be coupled to the first anatomical siteof the subject;

a second electrode, configured to be coupled to the second anatomicalsite of the subject; and

a control unit, configured to:

-   -   detect a pressure difference between the first and second        anatomical sites, and    -   in response to the detected pressure difference, drive fluid        between the first and second anatomical sites by applying a        treatment voltage between the first and second electrodes.

In an application, the control unit is configured to provide a restperiod during which the treatment voltage is not applied, and to apply,between the first and second electrodes, an opposite voltage that isopposite to the treatment voltage and that has a lower magnitude thanthe treatment voltage.

In an application, each electrode is insulated such that no portion ofthe electrode may be in electrical contact with any tissue of thesubject, and the control unit is configured to drive a capacitativecurrent between the first and second insulated electrodes by applyingthe treatment voltage between the electrodes.

In an application, the apparatus further includes a pressure sensor, andthe apparatus is configured to detect the pressure difference by thepressure sensor being configured to detect the pressure difference.

In an application, the pressure sensor includes a mechanical pressuresensor, configured to detect the pressure difference at least in part bydetecting mechanical pressure pressing on a component of the pressuresensor.

In an application, the pressure sensor includes at least a firstmechanical pressure sensor, configured to detect the pressure at thefirst anatomical site, and a second mechanical pressure sensor,configured to detect the pressure at the second anatomical site.

In an application, the apparatus is configured to detect the pressuredifference by detecting a voltage between the first and secondelectrodes, and the control unit is configured to apply the treatment inresponse to the detected pressure difference by being configured toapply the treatment voltage in response to the detected voltage.

In an application, the apparatus is configured to detect the detectedvoltage by being configured to detect a streaming voltage.

In an application, the apparatus is configured not to apply thetreatment voltage while detecting the detected voltage.

In an application, the control unit includes voltage-detectingcircuitry, configured to detect the voltage.

In an application, the first anatomical site includes a superiorsagittal sinus of the subject, the second anatomical site includes acerebral cortex of the subject, and the control unit is configured toelectroosmotically drive the fluid by electroosmotically driving thefluid between the superior sagittal sinus and the cerebral cortex of thesubject.

In an application, the control unit is configured to electroosmoticallydrive the fluid from the cerebral cortex to the superior sagittal sinusof the subject.

In an application, the control unit is configured to detect the pressureby being configured to detect a voltage between the first and secondelectrodes.

In an application, the first anatomical site includes a renal artery ofthe subject, the second anatomical site includes a ureter of thesubject, and the control unit is configured to configure the treatmentvoltage to electroosmotically drive the fluid by electroosmoticallydriving the fluid between the renal artery and the ureter of thesubject.

In an application, the control unit is configured to electroosmoticallydrive the fluid from the renal artery to the ureter of the subject.

In an application, the control unit is configured to detect the pressureby being configured to detect a voltage between the first and secondelectrodes.

In an application, the first anatomical site includes an artery enteringa lymph node of the subject, the second anatomical site includes amedullary sinus of the lymph node of the subject, and the control unitis configured to electroosmotically drive the fluid byelectroosmotically driving the fluid between the artery and themedullary sinus of the subject.

In an application, the control unit is configured to electroosmoticallydrive the fluid from the artery to the medullary sinus of the subject.

In an application, the control unit is configured to detect the pressureby being configured to detect a voltage between the first and secondelectrodes, and to apply the treatment voltage only when the detectedvoltage is greater than.

In an application, the first anatomical site includes a vitreous cavityof an eye of the subject, the second anatomical site includes aSchlemm's canal of the subject, and the control unit is configured toelectroosmotically drive the fluid by electroosmotically driving thefluid between the vitreous cavity and the Schlemm's canal of thesubject.

In an application, the control unit is configured to electroosmoticallydrive the fluid from the vitreous cavity to the Schlemm's canal of thesubject.

In an application, the control unit is configured to detect the pressureby being configured to detect a voltage between the first and secondelectrodes.

In an application, the first anatomical site includes a site within asubarachnoid cavity of the subject, the second anatomical site includesa site outside of the subarachnoid cavity of the subject, and thecontrol unit is configured to electroosmotically drive the fluid byelectroosmotically driving the fluid between the site within thesubarachnoid cavity and the site outside of the subarachnoid cavity ofthe subject.

In an application, the control unit is configured to electroosmoticallydrive the fluid from the site within the subarachnoid cavity to the siteoutside of the subarachnoid cavity of the subject.

In an application, the control unit is configured to detect the pressureby being configured to detect a voltage between the first and secondelectrodes.

There is further provided, in accordance with an application of thepresent invention, a method, including:

detecting a pressure difference between a first anatomical site and asecond anatomical site of a subject; and

in response to the detected pressure difference, electroosmoticallydriving fluid between the first and second anatomical sites by applyinga treatment voltage between the first and second anatomical sites.

In an application, the method further includes providing a rest periodduring which the treatment voltage is not applied, and applying, duringthe rest period, an opposite voltage between the first and secondanatomical sites, the opposite voltage being opposite to the treatmentvoltage and having a lower magnitude than the treatment voltage.

In an application, the method further includes implanting a firstelectrode at the first anatomical site, and implanting a secondelectrode at the second anatomical site, and applying the treatmentvoltage between the first and second anatomical sites includes applyingthe treatment voltage between the first and second electrodes.

In an application:

implanting the first electrode includes implanting a first insulatedelectrode, such that no portion of the first insulated electrode is inelectrical contact with any tissue of the subject,

implanting the second electrode includes implanting a second insulatedelectrode, such that no portion of the second insulated electrode is inelectrical contact with any tissue of the subject, and

applying the treatment voltage includes driving a capacitative currentbetween the first and second insulated electrodes.

In an application, detecting the pressure difference includes detectingthe pressure difference using at least one mechanical pressure sensor.

In an application, detecting the pressure difference includes detectinga pressure at the first anatomical site using a first mechanicalpressure sensor, and detecting a pressure at the second anatomical siteusing a second mechanical pressure sensor.

In an application, detecting the pressure difference includes detectingthe pressure difference by detecting a voltage between the first andsecond electrodes, and applying the treatment voltage in response to thedetected pressure difference includes applying the treatment voltage inresponse to the detected voltage.

In an application, detecting the detected voltage includes detecting astreaming voltage.

In an application, applying the treatment voltage includes not applyingthe treatment voltage while detecting the detected voltage.

In an application:

the first anatomical site includes a superior sagittal sinus of thesubject,

the second anatomical site includes a cerebral cortex of the subject,and

electroosmotically driving the fluid between the first and secondanatomical sites includes electroosmotically driving the fluid betweenthe superior sagittal sinus and the cerebral cortex of the subject.

In an application, driving the fluid between the superior sagittal sinusand the cerebral cortex of the subject includes driving the fluid fromthe cerebral cortex to the superior sagittal sinus of the subject.

In an application, detecting the pressure difference includes detectingthe pressure difference by detecting a voltage between the first andsecond electrodes.

In an application:

the first anatomical site includes a renal artery of the subject,

the second anatomical site includes a ureter of the subject, and

electroosmotically driving the fluid between the first and secondanatomical sites includes electroosmotically driving the fluid betweenthe renal artery and the ureter of the subject.

In an application, driving the fluid between the renal artery and theureter of the subject includes driving the fluid from the renal arteryto the ureter of the subject.

In an application, detecting the pressure difference includes detectingthe pressure difference by detecting a voltage between the first andsecond electrodes.

In an application:

the first anatomical site includes an artery entering a lymph node ofthe subject,

the second anatomical site includes a medullary sinus of the lymph nodeof the subject, and

electroosmotically driving the fluid between the first and secondanatomical sites includes electroosmotically driving the fluid betweenthe artery entering a lymph node and the medullary sinus of the subject.

In an application, driving the fluid between the artery entering thelymph node and the medullary sinus of the subject includes driving thefluid from the medullary sinus to the artery entering the lymph node ofthe subject.

In an application, detecting the pressure difference includes detectingthe pressure difference by detecting a voltage between the first andsecond electrodes.

In an application:

the first anatomical site includes a vitreous cavity of an eye of thesubject,

the second anatomical site includes a Schlemm's canal of the eye of thesubject, and

electroosmotically driving the fluid between the first and secondanatomical sites includes electroosmotically driving the fluid betweenthe vitreous cavity and the Schlemm's canal of the subject.

In an application, driving the fluid between the vitreous cavity and theSchlemm's canal of the subject includes driving the fluid from thevitreous cavity to the Schlemm's canal of the subject.

In an application, detecting the pressure difference includes detectingthe pressure difference by detecting a voltage between the first andsecond electrodes.

In an application:

the first anatomical site includes a nucleus pulposus of anintervertebral disc of the subject,

the second anatomical site includes a site outside of the nucleuspulposus of the disc of the subject, and

electroosmotically driving the fluid between the first and secondanatomical sites includes electroosmotically driving the fluid betweenthe nucleus pulposus and the site outside of the nucleus pulposus of thesubject.

In an application, driving the fluid between the nucleus pulposus andthe site outside of the nucleus pulposus of the subject includes drivingthe fluid from the nucleus pulposus to the site outside of the nucleuspulposus of the subject.

In an application, driving the fluid between the nucleus pulposus andthe site outside of the nucleus pulposus of the subject includes drivingthe fluid from the site outside of the nucleus pulposus to the nucleuspulposus of the subject.

In an application, detecting the pressure difference includes detectingthe pressure difference by detecting a voltage between the first andsecond electrodes.

In an application:

the first anatomical site includes a site within a subarachnoid cavityof the subject,

the second anatomical site includes a site outside of the subarachnoidcavity of the subject, and

electroosmotically driving the fluid between the first and secondanatomical sites includes electroosmotically driving the fluid betweenthe site within the subarachnoid cavity of the subject and the siteoutside of the subarachnoid cavity of the subject.

In an application, driving the fluid between the site within thesubarachnoid cavity and the site outside of the subarachnoid cavity ofthe subject includes driving the fluid from the site within thesubarachnoid cavity to the site outside of the subarachnoid cavity ofthe subject.

In an application, detecting the pressure difference includes detectingthe pressure difference by detecting a voltage between the first andsecond electrodes.

There is further provided, in accordance with an application of thepresent invention, a method, including:

electroosmotically driving fluid between a superior sagittal sinus of asubject and a cerebral cortex of the subject, by applying a treatmentvoltage between the superior sagittal sinus and the cerebral cortex ofthe subject.

In an application, the method further includes providing a rest periodduring which the treatment voltage is not applied, and applying, duringthe rest period, an opposite voltage between the superior sagittal sinusand the cerebral cortex, the opposite voltage being opposite to thetreatment voltage and having a lower magnitude than the treatmentvoltage.

In an application, applying the treatment voltage includes applying acapacitative current.

In an application, driving the fluid between the superior sagittal sinusand the cerebral cortex of the subject includes driving the fluid fromthe cerebral cortex to the superior sagittal sinus of the subject.

In an application, the method further includes detecting a pressuredifference between the superior sagittal sinus of the subject and thecerebral cortex of the subject, and applying the treatment voltageincludes applying the treatment voltage in response to the detectedpressure difference.

In an application, detecting the pressure difference includes detectinga voltage between the superior sagittal sinus of the subject and thecerebral cortex of the subject, and applying the treatment voltageincludes applying the treatment voltage in response to the detectedvoltage.

In an application, detecting the detected voltage includes detecting astreaming potential.

In an application, the method further includes implanting a firstelectrode at the superior sagittal sinus of the subject, and a secondelectrode at the cerebral cortex of the subject, and detecting thevoltage between the superior sagittal sinus of the subject and thecerebral cortex of the subject includes detecting a voltage between thefirst and second electrodes.

There is further provided, in accordance with an application of thepresent invention, a method, including:

electroosmotically driving fluid between a renal artery of a subject anda ureter of the subject, by applying a treatment voltage between therenal artery and the ureter of the subject.

In an application, the method further includes providing a rest periodduring which the treatment voltage is not applied, and applying, duringthe rest period, an opposite voltage between the renal artery and theureter, the opposite voltage being opposite to the treatment voltage andhaving a lower magnitude than the treatment voltage.

In an application, applying the treatment voltage includes applying acapacitative current.

In an application, driving the fluid between the renal artery and theureter of the subject includes driving the fluid from the renal arteryto the ureter of the subject.

In an application, the method further includes detecting a pressuredifference between the renal artery of the subject and the ureter of thesubject, and applying the treatment voltage includes applying thetreatment voltage in response to the detected pressure difference.

In an application, detecting the pressure difference includes detectinga voltage between the renal artery of the subject and the ureter of thesubject, and applying the treatment voltage includes applying thetreatment voltage in response to the detected voltage.

In an application, detecting the detected voltage includes detecting astreaming potential.

In an application, the method further includes implanting a firstelectrode at the renal artery of the subject, and a second electrode atthe ureter of the subject, and detecting the voltage between the renalartery of the subject and the ureter of the subject includes detecting avoltage between the first and second electrodes.

There is further provided, in accordance with an application of thepresent invention, a method, including:

electroosmotically driving fluid between an artery entering a lymph nodeof a subject and a medullary sinus of the lymph node of the subject, byapplying a treatment voltage between the artery and the medullary sinusof the subject.

In an application, the method further includes providing a rest periodduring which the treatment voltage is not applied, and applying, duringthe rest period, an opposite voltage between the artery and themedullary sinus, the opposite voltage being opposite to the treatmentvoltage and having a lower magnitude than the treatment voltage.

In an application, applying the treatment voltage includes applying acapacitative current.

In an application, driving the fluid between the artery entering thelymph node and the medullary sinus of the subject includes driving thefluid from the medullary sinus to the artery entering the lymph node ofthe subject.

In an application, the method further includes detecting a pressuredifference between the artery of the subject and the medullary sinus ofthe subject, and applying the treatment voltage includes applying thetreatment voltage in response to the detected pressure difference.

In an application, detecting the pressure difference includes detectinga voltage between the artery of the subject and the medullary sinus ofthe subject, and applying the treatment voltage includes applying thetreatment voltage in response to the detected voltage.

In an application, detecting the detected voltage includes detecting astreaming potential.

In an application, the method further includes implanting a firstelectrode at the artery of the subject, and a second electrode at themedullary sinus of the subject, and detecting the voltage between theartery of the subject and the medullary sinus of the subject includesdetecting a voltage between the first and second electrodes.

There is further provided, in accordance with an application of thepresent invention, a method, including:

electroosmotically driving fluid between a vitreous cavity of an eye ofa subject and a Schlemm's canal of the eye of the subject, by applying atreatment voltage between the vitreous cavity and the Schlemm's canal ofthe subject.

In an application, the method further includes providing a rest periodduring which the treatment voltage is not applied, and applying, duringthe rest period, an opposite voltage between the vitreous cavity and theSchlemm's canal, the opposite voltage being opposite to the treatmentvoltage and having a lower magnitude than the treatment voltage.

In an application, applying the treatment voltage includes applying acapacitative current.

In an application, driving the fluid between the vitreous cavity and theSchlemm's canal of the subject includes driving the fluid from thevitreous cavity to the Schlemm's canal of the subject.

In an application, the method further includes detecting a pressuredifference between the vitreous cavity of the subject and the Schlemm'scanal of the subject, and applying the treatment voltage includesapplying the treatment voltage in response to the detected pressuredifference.

In an application, detecting the pressure difference includes detectinga voltage between the vitreous cavity of the subject and the Schlemm'scanal of the subject, and applying the treatment voltage includesapplying the treatment voltage in response to the detected voltage.

In an application, detecting the detected voltage includes detecting astreaming potential.

In an application, the method further includes implanting a firstelectrode at the vitreous cavity of the subject, and a second electrodeat the Schlemm's canal of the subject, and detecting the voltage betweenthe vitreous cavity of the subject and the Schlemm's canal of thesubject includes detecting a voltage between the first and secondelectrodes.

There is further provided, in accordance with an application of thepresent invention, a method, including:

electroosmotically driving fluid between a site within a subarachnoidcavity of a subject and a site outside of the subarachnoid cavity of thesubject, by applying a treatment voltage between the site within thesubarachnoid cavity and the site outside of the subarachnoid cavity ofthe subject.

In an application, the method further includes providing a rest periodduring which the treatment voltage is not applied, and applying, duringthe rest period, an opposite voltage between the site within thesubarachnoid cavity and the site outside of the subarachnoid cavity, theopposite voltage being opposite to the treatment voltage and having alower magnitude than the treatment voltage.

In an application, electroosmotically driving the fluid by applying thetreatment voltage includes electroosmotically driving fluid between asite within a subarachnoid cavity of a subject that is asymptomatic ofAlzheimer's disease and a site outside of the subarachnoid cavity of thesubject, by applying a treatment voltage between the site within thesubarachnoid cavity and the site outside of the subarachnoid cavity ofthe subject that is asymptomatic of Alzheimer's disease.

In an application, applying the treatment voltage includes applying acapacitative current.

In an application, driving the fluid between the site within thesubarachnoid cavity and the site outside of the subarachnoid cavity ofthe subject includes driving the fluid from the site within thesubarachnoid cavity to the site outside of the subarachnoid cavity ofthe subject.

In an application, the method further includes detecting a pressuredifference between the site within the subarachnoid cavity of thesubject and the site outsider of the subarachnoid cavity of the subject,and applying the treatment voltage includes applying the treatmentvoltage in response to the detected pressure difference.

In an application, detecting the pressure difference includes detectinga voltage between the site within the subarachnoid cavity of the subjectand the site outside of the subarachnoid cavity of the subject, andapplying the treatment voltage includes applying the treatment voltagein response to the detected voltage.

In an application, detecting the detected voltage includes detecting astreaming potential.

In an application, the method further includes implanting a firstelectrode at the site within the subarachnoid cavity of the subject, anda second electrode at the site outside of the subarachnoid cavity of thesubject, and detecting the voltage between the site within thesubarachnoid cavity of the subject and the site outside of thesubarachnoid cavity of the subject includes detecting a voltage betweenthe first and second electrodes.

The present invention will be more fully understood from the followingdetailed description of applications thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a system for altering throughputof fluid in the brain of a subject, in accordance with some applicationsof the present invention;

FIG. 2 is a schematic illustration of a system for altering throughputof fluid in a kidney of a subject, in accordance with some applicationsof the present invention;

FIG. 3 is a schematic illustration of a system for altering throughputof fluid in a lymph node of a subject, in accordance with someapplications of the present invention;

FIG. 4 is a schematic illustration of a system for altering throughputof fluid in an eye of a subject, in accordance with some applications ofthe present invention;

FIG. 5 is a schematic illustration of a system for sensing of thedriving of fluid in an intervertebral disc of a subject, in accordancewith some applications of the invention;

FIG. 6 is a schematic illustration of a system for altering throughputof fluid in the brain of a subject, in accordance with some applicationsof the invention; and

FIG. 7 is a schematic illustration of a system for applying acapacitance-based current, in accordance with some applications of thepresent invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIG. 1, which is a schematic illustration ofmedical apparatus 10, comprising a first electrode 12, a secondelectrode 14 and a control unit 16, for altering throughput of fluid inthe brain of a subject, in accordance with some applications of theinvention. According to one application of the present invention,medical apparatus 10 is coupled to a brain 20 of the subject. Typically,first electrode 12 is implanted at a superior sagittal sinus 22 of thesubject. Typically, second electrode 14 is implanted at a cerebralcortex 24 of the subject. According to one application of the presentinvention, control unit 16 is configured to apply a treatment voltagebetween first electrode 12 and second electrode 14, and to configure thetreatment voltage to electroosmotically drive fluid from cerebral cortex24 to superior sagittal sinus 22. It is hypothesized that this drivingof the fluid reduces intracranial pressure (e.g., pressure in thebrain), and thereby may be used to treat a subject suffering fromelevated intracranial pressure, such as a subject suffering fromhydrocephalus or brain trauma. It is also hypothesized that, for someapplications, this driving of the fluid may be used to treat a subjectsuffering from normal pressure hydrocephalus.

Typically, control unit 16 applies the treatment voltage as a directcurrent (DC). For some applications of the invention, the control unitis configured to apply the treatment voltage according to a pre-selectedschedule, such as a duty cycle, such as for a few hours per day, such aswhen the subject is sleeping. For example, the control unit may beconfigured to be controlled and/or powered by an extracorporealcontroller, such as a controller comprising a wireless transmitter,disposed in and/or in the vicinity of the subject's bed. For someapplications, one or more rest periods during which the treatmentvoltage is not applied, are provided in the pre-selected schedule. It ishypothesized that for some applications, the rest period facilitatesequilibration of charge in the body of the subject. For some suchapplications, during rest periods in which the treatment voltage is notbeing applied, an opposite voltage (i.e., a voltage having an oppositesign to the treatment voltage) having a different (e.g., lower)magnitude is applied.

For some applications of the invention, apparatus 10 is configured todetect a pressure at least one of the electrodes (e.g., the pressureabove atmospheric pressure, at the implantation site of the electrode),and to apply the treatment voltage in response to the detected pressure.For example, apparatus 10 may be configured to detect pressure atcerebral cortex 24, and to apply the treatment voltage if the detectedpressure is greater than a threshold pressure.

For some applications of the present invention, apparatus 10 comprises apressure sensor 18, configured to detect the pressure. For someapplications of the invention, pressure sensor 18 comprises a mechanicaltransducer-based pressure sensor, as is known in the art. That is, forsome applications, the pressure sensor is configured to detect thepressure by detecting the mechanical pressure pressing on a component ofthe pressure sensor. For some such applications, and as shown in FIG. 1,pressure sensor 18 is coupled to and/or integrated with at least one ofthe electrodes, such as electrode 12.

For some applications, apparatus 10 is configured to sense a pressuredifference between the implantation sites of first electrode 12 andsecond electrode 14, and to apply the treatment voltage in response tothe detected pressure difference. For example, and as shown in FIG. 1,apparatus 10 may comprise two or more pressure sensors 18, each pressuresensor being coupled to and/or integrated with a respective electrode,and control unit 16 being configured to sense the difference between thepressure detected by each pressure sensor.

Alternatively or additionally, apparatus 10 may sense the pressuredifference by detecting a voltage, such as a streaming potential,between the electrodes, that is indicative of the pressure differencebetween the sites. For example, control unit 16 may comprisevoltage-detecting circuitry 17, configured to detect the voltage betweenelectrodes 12 and 14, and may be configured to apply the treatmentvoltage only if the detected voltage is greater than a thresholdvoltage. Typically, control unit 16 is configured to apply the voltageonly when the detected voltage between first electrode 12 and secondelectrode 14 is greater than 2 mV (e.g., greater than 20 mV, buttypically less than 500 mV, for example, less than 50 mV). For some suchapplications, apparatus 10 may be considered to comprise a pressuredetector that comprises electrodes 12 and 14, and circuitry 17.

Typically, the detected voltage is detected while the treatment voltageis not applied. For example, control unit 16 may be configured to applythe treatment voltage and detect the detected voltage in a sequence,and/or to periodically stop applying the treatment voltage so as todetect the detected voltage.

For some applications of the invention, control unit 16 comprises areceiver 19 (e.g., an antenna), which receives power wirelessly from anextracorporeal device, e.g., a mattress-based transmitter, or atransmitter coupled to a belt, hat, eyeglasses, or clothing item of thesubject. For some applications, receiver 19 of control unit 16 receivespower wirelessly from an implanted transmitter coupled to a power source(e.g., a battery). Alternatively or additionally, the control unitreceives power from a power source (e.g., a battery), which may be in acommon housing with the control unit.

Reference is now made to FIG. 2, which is a schematic illustration ofmedical apparatus 10, comprising generally the same components as shownin FIG. 1, being used to alter throughput of fluid in a kidney of asubject, in accordance with some applications of the invention.According to one application of the present invention, medical apparatus10 is coupled to a kidney 30 of the subject. Typically, first electrode12 is coupled to a renal artery 32 of the subject, and second electrode14 is coupled to a ureter 34 of the subject. According to oneapplication of the present invention, control unit 16 is configured toapply a voltage between first electrode 12 and second electrode 14, andto configure the voltage to electroosmotically drive fluid from renalartery 32 to ureter 34. It is hypothesized that this driving of thefluid is beneficial for subjects suffering from kidney disease and/orcongestive heart failure (CHF).

As described with reference to FIG. 1, for some applications, apparatus10 is configured to detect a pressure at least one of the electrodes(e.g., the pressure above atmospheric pressure, at the implantation siteof the electrode), and to apply the treatment voltage in response to thedetected pressure. As also described with reference to FIG. 1, for someapplications, apparatus 10 is configured to detect a pressure differencebetween the implantation sites of the electrodes, and to apply thetreatment voltage in response to the detected pressure difference. Asfurther described with reference to FIG. 1, for some such applications,apparatus 10 is configured to detect the pressure difference bydetecting a voltage, such as a streaming potential, between theelectrodes, that is indicative of the pressure difference between thesites. When apparatus 10 is implanted as shown in FIG. 2, the apparatusmay thereby be configured to detect the pressure at renal artery 32(e.g., the pressure above atmospheric pressure), and/or to detect thepressure difference and/or the voltage between the renal artery andureter 34, and to apply the treatment voltage if the detected pressure,pressure difference, and/or voltage is greater than a thresholdpressure, pressure difference, and/or voltage.

Typically, the detected voltage is detected while the treatment voltageis not applied. For example, control unit 16 may be configured to applythe treatment voltage and detect the detected voltage in a sequence,and/or to periodically stop applying the treatment voltage so as todetect the detected voltage.

Reference is now made to FIG. 3, which is a schematic illustration ofmedical apparatus 10 for altering throughput of fluid in a lymph node ofa subject, comprising generally the same components as shown in FIG. 1,in accordance with some applications of the invention. According to oneapplication of the present invention, medical apparatus 10 is coupled toa lymph node 40 of the subject. Typically, first electrode 12 is coupledto a blood vessel, such as an artery 42 (or similarly a vein), inproximity to (e.g., entering) lymph node 40 of the subject, and secondelectrode 14 is coupled to a medullary sinus 44 of the lymph node (or atanother site within the lymph node). According to one application of thepresent invention, control unit 16 is configured to apply a voltagebetween first electrode 12 and second electrode 14, and to configure thevoltage to electroosmotically drive fluid from medullary sinus 44 toward(e.g., into) artery 42.

As described with reference to FIG. 1, for some applications, apparatus10 is configured to detect a pressure at least one of the electrodes(e.g., the pressure above atmospheric pressure, at the implantation siteof the electrode), and to apply the treatment voltage in response to thedetected pressure. As also described with reference to FIG. 1, for someapplications, apparatus 10 is configured to detect a pressure differencebetween the implantation sites of the electrodes, and to apply thetreatment voltage in response to the detected pressure difference. Asfurther described with reference to FIG. 1, for some such applications,apparatus 10 is configured to detect the pressure difference bydetecting a voltage, such as a streaming potential, between theelectrodes, that is indicative of the pressure difference between thesites. When apparatus 10 is implanted as shown in FIG. 3, the apparatusmay thereby be configured to detect the pressure at medullary sinus 44(e.g., the pressure above atmospheric pressure), and/or to detect thepressure difference and/or the voltage between the medullary sinus andartery 42, and to apply the treatment voltage if the detected pressure,pressure difference, and/or voltage is greater than a thresholdpressure, pressure difference, and/or voltage.

Typically, the detected voltage is detected while the treatment voltageis not applied. For example, control unit may be configured to apply thetreatment voltage and detect the detected voltage in a sequence, and/orto periodically stop applying the treatment voltage so as to detect thedetected voltage.

Reference is now made to FIG. 4, which is a schematic illustration ofmedical apparatus 10, comprising generally the same components as shownin FIG. 1, for altering throughput of fluid in an eye of a subject, inaccordance with some applications of the invention. According to oneapplication of the present invention, medical apparatus 10 is coupled toan eye 50 of the subject. Typically, first electrode 12 is coupled to avitreous cavity 52, and second electrode 14 is coupled to Schlemm'scanal 54 of the subject. According to one application of the presentinvention, control unit 16 is configured to apply a voltage betweenfirst electrode 12 and second electrode 14, and to configure the voltageto electroosmotically drive fluid from vitreous cavity 52 to Schlemm'scanal 54 in order to reduce intraocular pressure.

As described with reference to FIG. 1, for some applications, apparatus10 is configured to detect a pressure at least one of the electrodes(e.g., the pressure above atmospheric pressure, at the implantation siteof the electrode), and to apply the treatment voltage in response to thedetected pressure. As also described with reference to FIG. 1, for someapplications, apparatus 10 is configured to detect a pressure differencebetween the implantation sites of the electrodes, and to apply thetreatment voltage in response to the detected pressure difference. Asfurther described with reference to FIG. 1, for some such applications,apparatus 10 is configured to detect the pressure difference bydetecting a voltage, such as a streaming potential, between theelectrodes, that is indicative of the pressure difference between thesites. When apparatus 10 is implanted as shown in FIG. 4, the apparatusmay thereby be configured to detect the pressure at vitreous cavity 52(e.g., the pressure above atmospheric pressure), and/or to detect thepressure difference and/or the voltage between the vitreous cavity andSchlemm's canal 54, and to apply the treatment voltage if the detectedpressure, pressure difference, and/or voltage is greater than athreshold pressure, pressure difference, and/or voltage.

Typically, the detected voltage is detected while the treatment voltageis not applied. For example, control unit 16 may be configured to applythe treatment voltage and detect the detected voltage in a sequence,and/or to periodically stop applying the treatment voltage so as todetect the detected voltage.

Reference is made to FIG. 5 which is a schematic illustration of medicalapparatus 10, comprising generally the same components as shown in FIG.1, for driving fluid in an intervertebral disc 60 of a subject, inaccordance with some applications of the invention. According to oneapplication of the present invention, medical apparatus 10 is coupled todisc 60 of the subject. Typically, first electrode 12 is implanted in anucleus pulposus 62 of the disc, and second electrode 14 is implanted ata site outside of the nucleus pulposus, such as coupled to an outersurface of an annulus fibrosus 64 of the disc. For some applications,electrode 12 comprises a rigid support element having a non-conductiveouter surface. The support element aids in the insertion of theelectrode through annulus fibrosus 64 into nucleus pulposus 62, and inholding the electrode in place upon insertion.

According to one application of the present invention, control unit 16is configured to apply a voltage between first electrode 12 and secondelectrode 14, and to configure the voltage to electroosmotically drivefluid from the site outside nucleus pulposus 62, into the nucleuspulposus. It is hypothesized that this driving of the fluid isbeneficial for subjects suffering from intervertebral disc fluid loss,by generally treating and/or preventing further degeneration in disc 60.Alternatively or additionally, control unit 16 may be configured toconfigure the voltage to electroosmotically drive fluid from the nucleuspulposus, to the site outside the nucleus pulposus.

As described with reference to FIG. 1, for some applications, apparatus10 is configured to detect a pressure at least one of the electrodes(e.g., the pressure above atmospheric pressure, at the implantation siteof the electrode), and to apply the treatment voltage in response to thedetected pressure. As also described with reference to FIG. 1, for someapplications, apparatus 10 is configured to detect a pressure differencebetween the implantation sites of the electrodes, and to apply thetreatment voltage in response to the detected pressure difference. Asfurther described with reference to FIG. 1, for some such applications,apparatus 10 is configured to detect the pressure difference bydetecting a voltage, such as a streaming potential, between theelectrodes, that is indicative of the pressure difference between thesites. When apparatus 10 is implanted as shown in FIG. 5, and isconfigured to drive fluid into the nucleus pulposus, the apparatus maythereby be configured to detect the pressure at nucleus pulposus 62(e.g., the pressure above atmospheric pressure), and/or to detect thepressure difference and/or the voltage between the nucleus pulposus andthe site outside of the nucleus pulposus, and to apply the treatmentvoltage if the detected pressure, pressure difference, and/or voltage issmaller than a threshold pressure, pressure difference, and/or voltage.

As described hereinabove, apparatus 10 may alternatively or additionallybe configured to drive fluid out of the nucleus pulposus. For suchapplications, the apparatus may thereby be configured to detect thepressure at the nucleus pulposus (e.g., the pressure above atmosphericpressure), and/or to detect the pressure difference and/or the voltagebetween the nucleus pulposus and the site outside of the nucleuspulposus, and to apply the treatment voltage if the detected pressure,pressure difference, and/or voltage is greater than a thresholdpressure, pressure difference, and/or voltage.

Typically, the detected voltage is detected while the treatment voltageis not applied. For example, control unit may be configured to apply thetreatment voltage and detect the detected voltage in a sequence, and/orto periodically stop applying the treatment voltage so as to detect thedetected voltage.

Reference is made to FIG. 6 which is a schematic illustration of medicalapparatus 10, comprising generally the same components as shown in FIG.1, for driving fluid in brain 20 of a subject, in accordance with someapplications of the invention. Typically, first electrode 12 isimplanted in a subarachnoid cavity 80 of the brain of the subject, andsecond electrode 14 is implanted at a site outside of the subarachnoidcavity, such as outside of the brain of the subject. For example, and asshown in FIG. 6, second electrode 14 may be integral with control unit16 (e.g., integral with a casing thereof), and control unit 16 may besubcutaneously implanted elsewhere in the body, such as at a site in thetorso of the subject. For some applications, first electrode 12 isplaced at a different site in the brain of the subject.

According to one application of the present invention, control unit 16is configured to apply a voltage between first electrode 12 and secondelectrode 14, and to configure the voltage to electroosmotically drivefluid out of subarachnoid cavity 80. It is further hypothesized by theinventor that the driving of the fluid is beneficial for subjectssuffering from and/or at risk of Alzheimer's disease (e.g., that areasymptomatic of Alzheimer's disease), by facilitation of clearance ofsubstances, such as amyloid-beta and metal ions (e.g., iron and copperions), from the brain of the subject. For example, reduction of theconcentration of amyloid beta monomers and/or oligomers from the brainmay (1) inhibit the formation and/or growth of amyloid-beta plaques inthe brain, and/or (2) reduce direct toxic effects of the oligomers onneurons of the brain. It is also hypothesized that, for someapplications, this driving of the fluid may be used to treat a subjectsuffering from normal pressure hydrocephalus.

It is further hypothesized by the inventor that the driving of the fluidreduces the volume of fluid in at least parts of the brain, such aswithin ventricles of the brain, suppressing enlargement of theventricles, e.g., caused by fluid pressure in the ventricles.

As described with reference to FIG. 1, for some applications, apparatus10 is configured to detect a pressure at least one of the electrodes(e.g., the pressure above atmospheric pressure, at the implantation siteof the electrode), and to apply the treatment voltage in response to thedetected pressure. As also described with reference to FIG. 1, for someapplications, apparatus 10 is configured to detect a pressure differencebetween the implantation sites of the electrodes, and to apply thetreatment voltage in response to the detected pressure difference. Asfurther described with reference to FIG. 1, for some such applications,apparatus 10 is configured to detect the pressure difference bydetecting a voltage, such as a streaming potential, between theelectrodes, that is indicative of the pressure difference between thesites. When apparatus 10 is implanted as shown in FIG. 6, the apparatusmay thereby be configured to detect the pressure at subarachnoid cavity80 (e.g., the pressure above atmospheric pressure), and/or to detect thepressure difference and/or the voltage between the subarachnoid cavityand the site outside of the subarachnoid cavity, and to apply thetreatment voltage if the detected pressure, pressure difference, and/orvoltage is greater than a threshold pressure, pressure difference,and/or voltage.

Typically, the detected voltage is detected while the treatment voltageis not applied. For example, control unit may be configured to apply thetreatment voltage and detect the detected voltage in a sequence, and/orto periodically stop applying the treatment voltage so as to detect thedetected voltage.

Reference is now made to FIG. 7, which is a schematic illustration ofmedical apparatus 100, for applying a capacitance-based current to asubject, in accordance with some applications of the invention.Typically, apparatus 100 comprises apparatus 10 and/or componentsthereof but, in apparatus 100, first electrode 12 and second electrode14 are insulated with an insulating material 102 (e.g., silicone).Typically, when control unit 16 applies a voltage between firstelectrode 12 and second electrode 14, a capacitance-based current flowsfrom first electrode 12 to second electrode 14, resulting in fluidelectroosmotically moving from a first site 72 in the body toward asecond site in the body. For example, this technique may be practiced toelectroosmotically drive fluid (e.g., to alter the throughput of fluid)between any of the sites described in FIGS. 1-6, mutatis mutandis. Forsome applications, insulating material 102 inhibits corrosion ofelectrodes 12 and/or 14. For some applications, only one of electrodes12 and 14 is insulated with insulating material 102.

Reference is again made to FIGS. 1-7. For some applications (e.g., asdescribed with reference to FIG. 5, mutatis mutandis), it may bedesirable to increase the pressure difference between the implantationsites of electrodes 12 and 14. For some such applications, the apparatusis thereby configured to detect the pressure (e.g., the pressure aboveatmospheric pressure), and/or to detect the pressure difference and/orthe voltage between the implantation sites, and to apply the treatmentvoltage if the detected pressure, pressure difference, and/or voltage issmaller than a threshold pressure, pressure difference, and/or voltage.

Reference is again made to FIGS. 1-7. For some applications, electrode12 and/or electrode 14 comprise more than one electrode, respectively,e.g., so as to distribute the treatment voltage over a larger region ofa tissue compared to a single electrode. For example, with respect tothe configuration shown in FIG. 1, a plurality of electrodes 14 may beimplanted in cerebral cortex 24, each of the electrodes 14 beingimplanted at a different region of the cerebral cortex, so as to drivefluid from each of the regions of the cerebral cortex toward superiorsagittal sinus 22. Similarly, for some applications, electrode 12 and/orelectrode 14 may comprise a large (e.g., elongate, planar, and/or amesh) electrode that is thereby configured to distribute the treatmentvoltage over a larger region of tissue compared to a smaller electrode.

Reference is again made to FIGS. 1-6. It is to be noted that FIGS. 1-6show examples of anatomical sites in which apparatus 10 may be used, andthat apparatus 10 may be used in anatomical sites (e.g., otheranatomical sites) that include a native membrane across which a pressuredifference exists.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

The invention claimed is:
 1. A method, comprising: implanting a first electrode within a subarachnoid cavity of a brain of a subject who is asymptomatic of Alzheimer's disease, and a second electrode outside of the subarachnoid cavity of the brain of the subject who is asymptomatic of Alzheimer's disease; and electroosmotically driving fluid between a site within the subarachnoid cavity of the brain of the subject and a site outside of the subarachnoid cavity of the brain of the subject who is asymptomatic of Alzheimer's disease, by applying a treatment voltage between the first and the second electrodes in order to reduce risk for developing Alzheimer's disease.
 2. The method according to claim 1, further comprising providing a rest period during which the treatment voltage is not applied, and applying, during the rest period, an opposite voltage between the first and the second electrodes, the opposite voltage being opposite to the treatment voltage and having a lower magnitude than the treatment voltage.
 3. The method according to claim 1, wherein applying the treatment voltage comprises applying a capacitative current.
 4. The method according to claim 1, wherein driving the fluid between the site within the subarachnoid cavity of the brain and the site outside of the subarachnoid cavity of the brain of the subject comprises driving the fluid from the site within the subarachnoid cavity of the brain to the site outside of the subarachnoid cavity of the brain of the subject.
 5. The method according to claim 1, further comprising detecting a pressure difference between the site within the subarachnoid cavity of the brain of the subject and the site outside of the subarachnoid cavity of the brain of the subject, and wherein applying the treatment voltage comprises applying the treatment voltage in response to the detected pressure difference.
 6. The method according to claim 1, wherein implanting the second electrode comprises implanting the second electrode outside of the brain of the subject.
 7. A method, comprising: implanting a first electrode within a subarachnoid cavity of a brain of a subject, and a second electrode outside of the subarachnoid cavity of the brain of the subject; electroosmotically driving fluid between a site within the subarachnoid cavity of the brain of the subject and a site outside of the subarachnoid cavity of the brain of the subject, by applying a treatment voltage between the first and the second electrodes; and detecting a pressure difference between the site within the subarachnoid cavity of the brain of the subject and the site outside of the subarachnoid cavity of the brain of the subject, wherein applying the treatment voltage comprises applying the treatment voltage in response to the detected pressure difference, wherein detecting the pressure difference comprises detecting a voltage between the site within the subarachnoid cavity of the brain of the subject and the site outside of the subarachnoid cavity of the brain of the subject, and wherein applying the treatment voltage comprises applying the treatment voltage in response to the detected voltage.
 8. The method according to claim 7, wherein the subject is asymptomatic of Alzheimer's disease, and wherein electroosmotically driving the fluid comprises electroosmotically driving fluid between the site within the subarachnoid cavity of the brain of the subject who is asymptomatic of Alzheimer's disease and the site outside of the subarachnoid cavity of the brain of the subject who is asymptomatic of Alzheimer's disease.
 9. The method according to claim 7, wherein detecting the detected voltage comprises detecting a streaming potential.
 10. The method according to claim 7, wherein detecting the voltage between the site within the subarachnoid cavity of the brain of the subject and the site outside of the subarachnoid cavity of the brain of the subject comprises detecting a voltage between the first and second electrodes.
 11. The method according to claim 7, further comprising providing a rest period during which the treatment voltage is not applied, and applying, during the rest period, an opposite voltage between the first and the second electrodes, the opposite voltage being opposite to the treatment voltage and having a lower magnitude than the treatment voltage.
 12. The method according to claim 7, wherein applying the treatment voltage comprises applying a capacitative current.
 13. The method according to claim 7, wherein driving the fluid between the site within the subarachnoid cavity of the brain and the site outside of the subarachnoid cavity of the brain of the subject comprises driving the fluid from the site within the subarachnoid cavity of the brain to the site outside of the subarachnoid cavity of the brain of the subject.
 14. The method according to claim 7, wherein implanting the second electrode comprises implanting the second electrode outside of the brain of the subject. 